The proposed research seeks to examine the factors that allow the transmission and amplification of antibiotic-resistant bacterial clones in the community. By examining the population dynamics of different strains of methicillin-resistant Staphylococcus aureus (MRSA) in the community, we will identify genotypic and clinical predictors for their persistent carriage and determine whether "community strains" do in fact behave differently from previously recognized healthcare-associated MRSA strains in the community environment. Resistance to the beta-lactam antibiotics is mediated by SCCmec (staphylococcal cassette chromosome), which has been recently shown to have four types. Multiple reports have suggested an association between SCCmec type IV and strains isolated from patients in the community without recognized risk factors for MRSA carriage; on the other hand, SCCmec type II (and I and III, though these are not prevalent at our institution) has been classically associated with healthcare-related strains of MRSA. We plan to use SCCmec type as a marker for MRSA strains. Further molecular studies will allow the distinction between the SCCrnec element and the remainder of the host bacterial chromosome; we will thus be able to investigate other potential genes that may contribute to increased fitness of different MRSA strains. This three-part study will consist of (1) a cross-sectional survey of all MRSA submitted as clinical specimens to the Clinical Microbiology Laboratory at our institution, to examine the relative proportions of SCCmec types in these isolates; (2) a case-control study of patients hospitalized with MRSA infection, to identify predisposing risk factors that may predict carriage of MRSA of the different SCCmec types; and (3) a cohort study of MRSA-colonized patients after hospital discharge, to determine whether SCCmec type predicts persistent colonization in the community. The applicant, Dr. Jose M. Eguia, is an infectious disease specialist with training in epidemiology. This proposal is intended to provide him with additional training in the essentials of molecular epidemiology and microbiology, advanced epidemiology and biostatistics, in the setting of a strong mentored research program. With these skills, he will be able to utilize classical and molecular epidemiology to investigate the microbiologic, clinical and ecologic factors responsible for the transmission of antibiotic resistant bacteria; this will lead to improved, rational methods of containing resistance, and thereby contribute to the public health.